title: A randomized controlled trial of venlafaxine XR for major depressive disorder after spinal cord injury: Methods and lessons learned.
abstract: OBJECTIVE
  We describe the rationale, design, methods, and lessons learned conducting a treatment trial for major depressive disorder (MDD) or dysthymia in people with spinal cord injury (SCI).
  
  
  METHODS
  A multi-site, double-blind, randomized (1:1) placebo controlled trial of venlafaxine XR for MDD or dysthymia. Subjects were block randomized and stratified by site, lifetime history of substance dependence, and prior history of MDD.
  
  
  METHODS
  Six SCI centers throughout the United States.
  
  
  METHODS
  Across participating centers, 2536 subjects were screened and 133 were enrolled into the trial. Subjects were 18-64 years old and at least 1 month post-SCI. Interventions Twelve-week trial of venlafaxine XR versus placebo using a flexible titration schedule.
  
  
  METHODS
  The primary outcome was improvement in depression severity at 12 weeks. The secondary outcome was improvement in pain.
  
  
  RESULTS
  This article includes study methods, modifications prompted by a formative review process, preliminary data on the study sample and lessons learned. We describe common methodological and operational challenges conducting multi-site trials and how we addressed them. Challenges included study organization and decision making, staff training, obtaining human subjects approval, standardization of measurement and treatment, data and safety monitoring, subject screening and recruitment, unblinding and continuity of care, database management, and data analysis.
  
  
  CONCLUSIONS
  The methodological and operational challenges we faced and the lessons we learned may provide useful information for researchers who aim to conduct clinical trials, especially in the area of medical treatment of depression in people with SCI.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Bombardier
authors.forename: Jesse R
authors.initials: JR
authors.lastname: Fann
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Wilson
authors.forename: Allen W
authors.initials: AW
authors.lastname: Heinemann
authors.forename: J Scott
authors.initials: JS
authors.lastname: Richards
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Warren
authors.forename: Larry
authors.initials: L
authors.lastname: Brooks
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Warms
authors.forename: Nancy R
authors.initials: NR
authors.lastname: Temkin
authors.forename: Denise G
authors.initials: DG
authors.lastname: Tate
mesh_terms: D000293:Adolescent; D000328:Adult; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods; D010146:Pain / Q000209:etiology / Q000517:prevention & control* / Q000523:psychology; D012107:Research Design; D013119:Spinal Cord Injuries / Q000150:complications* / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000069470:Venlafaxine Hydrochloride
keywords: Antidepressants; Dysthymia; Major depressive disorder; Pain; Randomized controlled trials; Research design; Spinal cord injuries